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C-Reactive Protein Levels Are Not Associated with Increased Risk for Colorectal Cancer in Women

Shumin M. Zhang, MD, ScD; Julie E. Buring, ScD; I-Min Lee, MBBS, ScD; Nancy R. Cook, ScD; and Paul M. Ridker, MD, MPH
[+] Article and Author Information

From Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts.


Acknowledgments: The authors thank Marilyn Chown for her statistical analytic support, the staff of the Women's Health Study, and the 39 876 dedicated participants of the Women's Health Study.

Grant Support: By research grants CA-47988 and HL-43851 from the National Institutes of Health, with additional support from the Doris Duke Foundation and the Donald W. Reynolds Foundation. Dr. Zhang is supported in part by a National Cancer Institute Career Development Award (CA096619).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Shumin M. Zhang, MD, ScD, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215; e-mail, shumin.zhang@channing.harvard.edu.

Current Author Addresses: Drs. Zhang, Buring, Cook, Lee, and Ridker: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215.

Author Contributions: Conception and design: S.M. Zhang, P.M. Ridker.

Analysis and interpretation of the data: S.M. Zhang, N.R. Cook, P.M. Ridker.

Drafting of the article: S.M. Zhang, P.M. Ridker.

Critical revision of the article for important intellectual content: S.M. Zhang, J.E. Buring, I.-M. Lee, N.R. Cook, P.M. Ridker.

Final approval of the article: S.M. Zhang, J.E. Buring, I.-M. Lee, N.R. Cook, P.M. Ridker.

Statistical expertise: S.M. Zhang, N.R. Cook, P.M. Ridker.

Obtaining of funding: J.E. Buring, P.M. Ridker.

Administrative, technical, or logistic support: S.M. Zhang, I.-M. Lee, P.M. Ridker.

Collection and assembly of data: S.M. Zhang, J.E. Buring, I.-M. Lee, P.M. Ridker.


Ann Intern Med. 2005;142(6):425-432. doi:10.7326/0003-4819-142-6-200503150-00008
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Through 20 February 2004, 169 incident cases of invasive colorectal adenocarcinoma were confirmed: 70 cases of proximal colon cancer, 59 cases of distal colon cancer, 36 cases of rectal cancer, 3 cases with overlapping lesions in the colon, and 1 case of colon cancer in which the site was not specified. Median and maximum lengths of follow-up were 10.1 and 10.8 years, respectively. Age at diagnosis of colorectal cancer cases ranged from 47 to 86 years (mean, 65 years). The incidence rate of colorectal cancer among the 27 913 women for the current analysis was 63.1 cases/100 000 person-years, which was similar to the rate in the entire cohort of the Women's Health Study (62.7 cases/100 000 person-years). Median values of baseline plasma CRP were 2.02 mg/L among all 27 913 women, 1.43 mg/L among the 12 910 women who had never used postmenopausal hormones at baseline, and 2.60 mg/L among the 14 949 women who had ever used postmenopausal hormones at baseline. The median value of baseline plasma CRP was 1.77 mg/L for the 169 colorectal cancer cases diagnosed during follow-up. Baseline CRP levels were higher for the 27 colorectal cancer cases diagnosed within the first 2 years of follow-up (median, 2.63 mg/L). Median values of baseline plasma CRP were 1.17 mg/L among the 81 patients with colorectal cancer who had never used postmenopausal hormones at baseline and 1.39 mg/L among the 11 patients with colorectal cancer who received the diagnosis within the first 2 years of follow-up and had never used postmenopausal hormones at baseline.

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Comments

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Diabetes and colorectal cancer
Posted on March 19, 2005
Luca Mascitelli
Comando Brigata alpina "Julia"
Conflict of Interest: None Declared

TO THE EDITOR: Zhang and colleagues reported that C-reactive protein levels were not significantly associated with increased risk for developing colorectal cancer in women (1). However, they did not consider diabetic status in the studied population. There is a growing body of evidence that type 2 diabetes mellitus is associated with increased risk of colorectal cancer (2-4). Furthermore, elevated glycated hemoglobin concentrations, even at levels below those used for diagnosis of diabetes, have been shown to be associated with increased colorectal cancer risk (5). Thus, abnormal glucose metabolism might have been a confounder in this study (1).

Luca Mascitelli, MD Comando Brigata alpina "Julia" Udine, Italy 33100

Francesca Pezzetta, MD Ospedale di San Vito al Tagliamento San Vito al Tagliamento, Italy 33078

REFERENCES

1. Zhang SM, Buring JE, Lee IM, Cook NR, Ridker PM. C-reactive protein levels are not associated with increased risk for colorectal cancer in women. Ann Intern Med. 2005;142:425-32.

2. Will JC, Galuska DA, Vinicor F, Calle EE. Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 1998;147:816-25.

3. Hu FB, Manson JE, Liu S, Hunter D, Colditz GA, Michels KB, et al. Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst. 1999;91:542-7.

4. Kaaks R, Toniolo P. Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, et al. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000;92:1592-600.

5. Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev. 2004;13:915-9.

Conflict of Interest:

None declared

In Response
Posted on May 6, 2005
Shumin M Zhang
Brigham and Women's Hospital
Conflict of Interest: None Declared

To the Editor:

We thank Mascitelli and Pezzetta for their interest in our paper. They suggest that abnormal glucose metabolism might be responsible for the null association between C-reactive protein (CRP) levels and risk of colorectal cancer that we observed (1). We conducted an analysis excluding 681 women who reported a history of diabetes mellitus at baseline from our study population, and the associations between C-reactive protein and risk of colorectal cancer did not appreciably change. The multivariable hazard ratios and their corresponding 95% confidence intervals according to cutoff points for CRP were 0.74 (0.49 to 1.11) for the category of 1 to 3 mg/L and 0.66 (0.42 to 1.03) for the category of greater than 3 mg/L (P for trend = 0.12), compared with the category of less than 1 mg/L. These data suggest our findings are unlikely to be explained by confounding by diabetes mellitus.

Shumin M. Zhang, MD, ScD Assistant Professor of Medicine and Epidemiology Division of Preventive Medicine, shumin.zhang@channing.harvard.edu

Paul M Ridker, MD, MPH

Brigham and Women's Hospital Boston, MA 02215

References:

1. Zhang SM, Buring JE, Lee IM, Cook NR, Ridker PM. C-reactive protein levels are not associated with increased risk for colorectal cancer in women. Ann Intern Med. 2005;142:425-32.

Conflict of Interest: None declared

Conflict of Interest:

None declared

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Summary for Patients

Can a Blood Test Help Predict Who Is at Risk for Colorectal Cancer?

The summary below is from the full report titled “C-Reactive Protein Levels Are Not Associated with Increased Risk for Colorectal Cancer in Women.” It is in the 15 March 2005 issue of Annals of Internal Medicine (volume 142, pages 425-432). The authors are S.M. Zhang, J.E. Buring, I.-M. Lee, N.R. Cook, and P.M. Ridker.

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